Process of preparing n, o-dimethylhydroxylamine



United States Patent ()fifice 3,337,631

Patented Aug. 22, 1967 3 337 631 tion with a palladium on carboncatalyst and hydrogen gas under 20 to 60 pounds per square inch gauge ofpres- PROCESS sure. A11 acid such as oxalic should be: present to takeup duct Henry J. Gergovlch Wilmington and Donald L. Smathers the Nmethylhydroxylamme f folms as a PI Claymont, DeL, iissignors to I. duPont de Nemours The i y i 1S freed from i acld and Company, Wilmington,DeL, acorporation otDelaby the addition of a suitable base such assodium hy- Ware droxide and is then reacted with the substitutedcarbonyl No Drawing. Original application Mar. 7, 1961, Ser. No.compound as shown above. The hydroxylamine is of 93,849, How Patent3,178,467, dated P 13, 1965- course in aqueous solution as a result ofthe hydrogenaand this application June 1964 tion and the substitutedaldehyde or ketone is simply stirred into it to produce thecorresponding nitrone. 2 Claims (CL 260 583) The aldehyde or ketone isdetermined by the R and This application is a divisional application ofy R substituents to be present in the novel N-alpha-sub- Copeiidingapplication 93,849 flied 196i, stituted-alkylidene-N-R-oXy-N-methylammoniurn salts of 110W Patent the invention. The aldehydeor ketone is regenerated This invention Ieiates to the Preparation of inthe process and is recycled. Additional aldehyde or methyihydl'oxyiamineand homoioglles and is more P ketone can be added as required to make uplosses.

directed to processes for making such amines The'particular ketone ofaldehyde employgd is unbeginning With all alpha Substituted N-methyiiiiifonfi' important in the processes of the invention. As will be Theinvention is further directed to N-alpha-substituted- Seen f om th fl wdiagram above the aqueous cleavage y ay- -methylammonium salts.separates out the ketone or aldehyde, whatever its char- PrOcesses ofthe invention can be illustrated generally acter, and it does not enterinto the final product proin the following diagram: duced. It istherefore quite unimportant in terms of the 1 CH N0 nitromethane lreduce 2 CH NHOH N-mebhylhydroxylamine C N CH alpha substituted r BN-methyl nitrone e 0 y quaternization c l 0R N-a1phasubstitutedt .e R la1kyl1dene- C N CH X N-R -oxy-N-methyl- R ammonium salt aqueous cleavage5 CH NH0R N-methyl- 0-11 hydroxylamine where a production ofN-methyl-O-R hydroxylamine what ketone R:= hydrogen or an alkyl group of1 through 4 carbon or aldehydeis employed Ketones and aldehydes whichcan be used, as indicated atoms, R =hydrogen, an alkyl group of 1through 4 carbon above Include the fonOWmg:

atoms, phenyl, tolyl, monochloro or dichlorophenyl, (1) formaldehydenitro phenyl or furyl groups, or R and R taken to- (2) acetaldehydegether=cyclohexyl or cyclopentyl rings, (3) propionaldehyde Rg=alkyl oralkenyl groups of 1 through 4 carbon atoms, (4) butyraldehy-de X =alkylsulfates of 1 to 4 carbon atoms, benzenesulfovalerflidehyde nate,toluenesulfonate, chloride, iodide, or bromide. beflzaidehyde (7) ortho,meta, para-tolualdehyde 'Pmducnon of the mtmne (8) ortho, meta,para-chlorobenzaldehyde The nitrone employed as a starting material canbe 5 (9) dichlorobenzaldehyde prepared in any convenient way. Asillustrated above (10) furfuraldehyde nitromethane can be reduced as bycatalytic hydrogena- (l1) ortho, meta, para, nitrobenzaldehyde acetonemethyl ethyl ketone diethyl ketone acetophenone propiophenonecyclopentanone cyclohexanone Preparation ofN-aZpha-substituted-alkylidene-N-R oxy-N-methylammonium salt Accordingto the invention a nitrone of the type above described resulting fromthe particular ketone or aldehyde employed is quaternized by treatmentunder anhydrous conditions and at a temperature from 35 to 110 C.

The quaternizing agents employed are those which have the structure R Xwhere X has the value above described. Thus there can be usedmethylating agents such as dimethylsulfate, methylchloride, methyliodide, methyl bromide, methyl benzenesulfonate, methylparatoluenesulfonate.

Other quaternizing agents which can be employed include diethyl sulfate,d-ipropyl sulfate, dibutyl sulfate, allyl chloride, allyl bromide,methallyl chloride, allyl benzenesulfonate, allyl toluenesulfonate,butyl benzenesulfonate, Z-butenyl benzenesulfonate, propyltoluenesulfonate.

The amount of the quaternizing agent will ordinarily be a molecularlyequivalent to the nitrone. There is no advantage to using an excess butno great disadvantage. 'It is enough that approximately one mol be used.

Quaternization is conducted in a substantially anhydrous condition sinceany water present usually results in a loss of yield. The reaction canbe conducted between the nitrone and the quaternizing agent in a meltedcondition or the reaction can be conducted in a mutual solvent.

The solvents can be any of those mentioned earlier for the nitrone andadditionally there can be used:

benzene dibu tylether carbon tetrachloride dichlorobenzene Xylenedioxane. chlo r-obenzene The amount of solvent is almost immaterial.Enough should be used to give a fluid system but no .great excess shouldbe used because of expense, both of solvent and handling equipment.

The quaternizat-ion can be conducted over a considerable range oftemperatures from room temperature or slightly above up to thedecomposition point of one of the components or the end product.Generally if the contents are to be molten, higher temperatures will beused up to 150 to even 200 C. and of course a quaternizing agent such asmethyl chloride or another volatile material would not remain in thesystem unless it were contained under pressure.

It is preferred to employ somewhat lower temperatures ranging from about35 to 110 C. and ordinarily a temperature as low as will give areasonable rate of reaction is preferred.

It will be understood that the N-alpha-substituted-alkylidene-N-R-oxy-N-methylammon-ium salts will be those having the R, R and Rsubstituents as above described in connection with the quaternizingagent and the aldehydes and ketones. Examples of such salts are givenbelow:

(1) N-benzylidene-N-ethoxy-N-methy1ammonium ethosulfate (2) N-methylN-(p-methylbenzylidene) ammonium proposulfate (3)N-n-butoxy-N-(o-chlorobenzylidene) -N-methylammonium butosulfate (4)N-(p-chloro-a-methylbenzylidene)-N-methyl-N- vinyloxyammoniump-toluenesulfonate (5 N-(2-furfurylidene)-N-methoxy-N-methylammoniumchloride (6) N-allyloxy-N- (2,4-dichloro-a-ethylbenzylidene) -N-methylammonium bromide (7) N- Z-butenoxy -N-(m-chloro-a-propylbenzylidene N-methylammonium chloride (8) N-3,4-dichlorobenzylidene -N-methyl-N-propenoxyammonium benzenesulfonate(9) N-methoxy-N-methyl-N(m-nitrobenzylidene) ammonium iodide 10)N-methyl-N-(o-methylbenzylidene) -N-iso-propenoxyammoniumo-toluenesulfonate 1 1) N-methyl-N- (p-nitrobenzylidene)-N-iso-propoxyammonium iodide (12) N-sec-butoxy-N-methylN-(m-methylbenzylidene) ammonium bromide (13)N-iso-butoxy-N-methyl-N-(a-methylbenzylidene) ammonium chloride (14)Nbutylidene-N-methoxy-N-methylammonium methosulfate 15N-iso-propylidene-N-methoxy-N-methylammonium iodide 16) N-(Z-butylidene)-N-ethoxy-N-methylammonium bromide (17) N-( 3 -hexylidene-N-methyl-N-n-propoxyammonium p-toluenesulfonate l8) Bis-(N-2-hexylidene-N-methoxy-N-methylammonium) sulfate 19)N-cyclohexylidene-N-methoXy-N-methylammonium methosulfate (20)N-cyclopentylidene-N-methoxy-N-methylammonium iodide N-n-propoxy- Theaqueous cleavage It is remarkable that theN-alpha-substituted-alkylidene-N-R oxy-N-methylammonium salts of theinvention are readily split up by the simple addition of one or moremolecular equivalents of water to produce N- methylO-R -hydroxylamineswith concurrent regeneration of the carbonyl compound corresponding tothe starting nitrone. These two can be separated in any convenientmanner, examples of which will be given hereinafter. Thus they can beseparated by extraction.

Sulfuric acid, hydrochloric acid, or another mineral acid can, ifdesired, be added to the water. It is thought that the acid keeps theamine in aqueous solution. The amount of acid can vary from 0.01 to 2mols based upon the weight of amine.

The N-methyl-0-R -hydroxylan1ine compounds and more particularlyN,O-dimethylhydroxylamine can be converted to a desired urea by reactionwith an appropriate isocyanate. Thus if a 3,4-dichlorophenylisocyanateis used with N,O-dimethylhydroxylamine one obtains 1-(3,4-dichlorophenyl)-3-methyl-3-methoxyurea. Other R oxy ureas andespecially the methoxyureas of U.S. Patent 2,960,534 issued Nov. 15,1960 to Otto Scherer and Paul Heller can similarly be prepared using theappropriate isocyanate.

In order that the invention may be better understood reference should behad to the following illustrativeexamples:

EXAMPLE 1 According to a preferred practice of the invention, N-benzylidene N-methoxy N-methylammonium methosulfate is prepared and fromit by aqueous cleavage there is prepared N,O-dimethylhydroxylamineaccording to the following scheme:

1. CH NO nltromethane reduce 2 CH NHOH o O cu=i-cu N-methylhydroxylaminefiltered to remove the catalyst and transferred to a vessel equippedwith a stirrer.

Forty parts by weight of sodium hydroxide as a 50% aqueous solution isadded and stirred into the product.

It is preferred not to permit the temperature to rise in the stirredvessel to a high figure and should be kept below, say, C. though this isnot critical. Particularly if solid sodium hydroxide is used there is aconsiderable tendency for the temperature to rise.

Eighty-five parts by weight of benzaldehyde is added and the mixture isstirred for about ten minutes. At this time the reaction is essentiallycomplete.

The reaction mixture is successively extracted with 4 aliquots ofchloroform each of which is about one-fourth the volume of the solutionbeing treated. The combined chloroform extracts are dried over sodiumsulfate and evaporated to dryness. The product thus produced is thenitrone shown above in Formula 3.

Quaternization of the nitrone 250 parts by weight of toluene and 101parts by weight of dimethylsulfate are added to 108 parts by weight ofthe nitrone prepared as above. The slurry is warmed gradually and aclear solution is obtained as the temperature rises. The temperature israised to about 75 C. It is to be noted that as the product forms thesolution again becomes cloudy. Heating is continued until the solutionbegins to boil. Heating is then discontinued. The solution is thenallowed to cool.

The resulting solution is chilled and the vessel is scratched or seededto promote crystallization of the prodnot. The product is then separatedand can be stored if kept dry.

The yield based on the nitrone is substantially 100%, the only majorloss being material retained on the equipment.

The aqueous cleavage 100 parts by weight of the product prepared asabove is treated with an equal weight of water at 40 C. The watercontains sulfuric acid in the amount of 15 parts H by weight.

The solution as produced is extracted with twice its volume of tolueneto remove the benzaldehyde. This can then be returned to the reaction.The remaining aqueous solution is adjusted to pH 6-7 and the amine isrecovered by distillation.

EXAMPLE 2 One hundred thirty-five parts by weight of alpha-phenyl-N-methyl nitrone, parts by weight of o-dichlorobenzene, and 60' parts byweight of methyl chloride are charged to a vessel equipped for pressureoperation. The vessel is sealed, the temperature is raised to C. andheld for three hours. The vessel is cooled and vented. The product, ifnot already crystalline, is crystallized by cooling and scratching andthen recovered by filtration. TheN-benzylidene-N-methoxy-N-methylammonium chloride thus produced can behydrolyzed in the manner described in Example 1 to produceN,O-dimethylhydroxy1- amine.

EXAMPLE 3 Eighty-seven parts by weight of alpha-alpha,N-trimethylnitrone and 126 parts by weight of dimethylsulfate are mixed and held at4550 C. for one hour. The N- iso-propylidene N-methoxy-N-methylammoniummethosulfate thus produced is crystallized by cooling and scratching.

Two hundred thirteen parts by weight of the product is treated with anequal weight of water containing 5 parts H 80 by weight at 30 C. forone-half hour. The resulting clear solution is adjusted to pH 6-7 andN,O*- dimethylhydroxylamine is distilled out first, followed by theacetone. The latter is then recycled.

an N-methyl,o-R -hydroxylamine.

8 R is selected from the group consisting of hydrogen and alkyl of 1through 4 carbon atoms; R is selected from the group consisting ofhydrogen, alkyl of 1 through 4 carbon atoms, phenyl, tolyl,monochlorophenyl, dichlorophenyl, nitrophenyl and furyl; and

R and R taken together are selected from the ,group consisting ofcyclohexyl and cyclopentyl and adding water to eifect aqueous cleavagethus producing N,O-dirnethylhydroxylamine.

Ex. R R R; X Quaternizing Conditions N-Methyl-O-Substituted NHydroxylamine c g Phenyl Hydrogen Ethyl Ethosulfate. 80 0.; hour; nosolvent Nmethyl-O-ethylhydroxylamine p-Tolyl do n-Propyl Proposulfate"100 0.; hour; dioxane solvent N-methyl-O-n-propylhydroxylamineo-0hlorophenyl do n-Butyl Butosulfate-.. 110 0.; 1 hour; toluene solventN-methyl-O-n-butylhydroxylamine p 0hlorophenyl Methyl Vinyl p-Tolfuen?60 0.; 3 hours; chloroform solvent N-methyl-O-vinylhydroxylamine su onee. Z-Iuryl Hydrogen-" Methyl Chloride 140 0.; 3% hours; xylene solventO-N-dirnethylhydroxylamine 2,4-diehlorophenyl... Ethyl Allyl Bromide 0.;10 hours; carbon tetra- Nmethyl-O-allylhydroxylamine chloride solvent.m-0hlorophenyl Propyl 2-butenyl Chloride 60 0.; 2 hours; tetrachloro-N-methyl-O-(2-butenyl)hydroxethylene solvent ylamine3,4-dichlorophenyl... Hydrogen PropenyL l Benzene- 0.; 8 hours;methylene chlor- N-methyl-O-propenylhydroxylsulfonate. ide solvent.m-Nitrophenyl do Methyl Iodide 84 (13.; 5thours; trichloroethyleneO,N-din1ethylhydroxylam1ne so ven o-Tolyl do Isopropenyl... o-Toluene-74 0.; 2 hours; trichloroethane N-methyl-O-isopropenylhydroxsulfonate.solvent. ylamine. p-Nitrophenyl iso-Propyl. Iodide 135 0.; 4 hours;xylene solvent N-methyl-O-iso-propylhydroxylamine m-Tolyl see-Butyl--Bromide 142 0.; 3 hours; dibutyl-ether N-methyl-O-secbutylhydroxylsolvenamine. Phenyl iso-Butyl. Chloride 135 0.; 5 hours; ehlorobenzeneN-methyl-O-iso-butylhydroxy1- solvent. amine Hydrogen MethylMethosuh'ate 40 0.; 2 hours; no solvent O,N-dimethylhydroxylamine Meth dIodide 80 0.; 5 hours; benzene solvent..- Do.

Bromide 38 0.; 8 hours; no solvent N-n1ethyl-0-ethylhydroxylamlnep-Toluene- 60 0 3 hours; chloroform solvent-N-methyl-O-n-propylhydroxylsulionate. amine Butyl Methyl Sulfate 0.; 4hours; no solvent O,N-dimethylhydroxylamine Pentamethylene Methosulfate.0.; hour; no solvent Do. Tetramethylene Iodide 0.; 4 hours; dioxanesolvent... Do.

The invention claimed is:

where 2. The process of claim 1 R is phenyl.

wherein R is hydrogen and References Cited UNITED STATES PATENTS 9/1965Levy 260583 X CHARLES B. PARKER, Primary Examiner.

R. L. RAYMOND, Assistant Examiner.

1. IN A PROCESS FOR MAKING N,O-DIMETHYLHYDROXYLAMINE THE STEPSCOMPRISING METHYLATING A NITRONE